Copper is an important element that is very important for the health of all living things (human, plant, animal, and microorganisms). In humans, copper is essential for the proper functioning of organs and metabolic processes. The human body has a complex homeostatic mechanism that seeks to ensure a constant supply of available copper, while removing excess copper whenever this occurs. However, like all the essential elements and nutrients, too much or too little consumption of copper nutrients can result in a condition of excess or lack of suitable copper in the body, each of which has a unique negative health effect.
Daily dietary standards for copper have been established by various health agencies around the world. Standards adopted by some countries recommend different levels of copper intake for adults, pregnant women, infants, and children, according to varying copper requirements during different stages of life.
Deficiency and copper toxicity may be of genetic or non-genetic origin. The study of copper genetic disease, which is the focus of intensive international research activities, has given insight into how the human body uses copper, and why it matters as an essential micronutrient. The study has also resulted in successful treatments for genetic copper excess conditions, allowing patients whose lives are threatened to live long and productively.
Researchers specializing in the field of microbiology, toxicology, nutrition, and health risk assessment work together to determine the exact level of copper required for essentiality, while avoiding deficient or excess copper intake. The results of this study are expected to be used to refine the government's dietary recommendations program designed to help protect public health.
Video Copper in health
Essentiality
Copper is an essential trace element (ie, micronutrients) necessary for plants, animals, and human health. It is also necessary for the normal functioning of aerobic microorganisms (requiring oxygen).
Copper is incorporated into various proteins and metalloenzymes that perform important metabolic functions; micronutrients are necessary for proper growth, development, and maintenance of bone, connective tissue, brain, heart, and many other organs. Copper is involved in the formation of red blood cells, the absorption and utilization of iron, the metabolism of cholesterol and glucose, and the synthesis and release of proteins and enzymes that sustain life. This enzyme in turn produces cell energy and regulates the transmission of nerves, blood clots, and oxygen transport.
Copper stimulates the immune system to fight infections, repair injured tissue, and promote healing. Copper also helps neutralize "free radicals", which can cause severe damage to cells.
The essence of copper was first discovered in 1928, when it was demonstrated that mice fed the copper-deficient milk diet could not produce enough red blood cells. Anemia is corrected by the addition of ash containing copper from vegetable or animal sources.
As an important element, daily dietary requirements for copper have been recommended by a number of government health agencies around the world.
Fetus, baby, and children
Copper is essential for the normal growth and development of human fetuses, infants, and children. Human fetus accumulates copper rapidly in the liver during the third trimester of pregnancy. At birth, healthy babies have four times the concentration of copper than adults. Breast milk is relatively low in copper, and the neonate liver shop falls rapidly after birth, supplying copper to the fast-growing body during breastfeeding. These supplies are needed to perform metabolic functions such as cellular respiration, melanin pigment and connective tissue synthesis, iron metabolism, free radical defense, gene expression, and normal function of the heart and immune system in infants.
Infants have special biochemical mechanisms to adequately manage copper in their bodies while a permanent lifetime mechanism develops and matures.
Severe copper deficiency in pregnant women increases the risk of health problems in the fetus and their baby. Health effects recorded include low birth weight, muscle weakness, and neurological problems. However, copper deficiency in pregnant women can be avoided with a balanced diet.
Because the availability of copper in the body is hindered by excess iron and zinc intake, pregnant women providing iron supplements to treat anemia or zinc supplements to treat colds should consult a doctor to ensure that the prenatal supplements they are taking also have significant nutrients. number of copper.
When newborns are breastfed, the baby's heart and breast milk provide enough copper for the first 4-6 months of life. When the baby is weaned, a balanced diet should provide a sufficient source of copper.
Cow's milk and some older infant formulas are drained in copper. Most formulas are now enriched with copper to prevent thinning.
The most nutritious children either have enough copper intake. Children who are compromised by health, including those who are premature, malnourished, have low birth weight, suffer from infections, and who experience increased rapid growth, are at high risk for copper deficiency. Fortunately, the diagnosis of copper deficiency in children is clear and reliable when conditions are suspected. Supplements under doctors' supervision usually facilitate full recovery.
Homeostasis
Copper is absorbed, transported, distributed, stored, and expelled in the body according to complex homeostatic processes that ensure a constant and sufficient supply of micronutrients while avoiding excess levels. If an insufficient amount of copper is digested for a short time, the storage of copper in the liver will be exhausted. If this depletion persists, a copper health deficiency condition may occur. If too much copper is swallowed, excessive conditions may occur. Both of these conditions, deficiencies and overloads, can cause tissue injury and disease. However, due to homeostatic regulation, the human body is able to balance various copper intakes for the needs of healthy individuals.
Many aspects of copper homeostasis are known at the molecular level. The essence of copper is due to its ability to act as an electron donor or acceptor as a flux oxidation state between Cu 1 (copper) and Cu 2 (cupric). As a component of about a dozen cuproenzymes, copper is involved in key redox (ie, oxidation-reduction) reactions in important metabolic processes such as mitochondrial respiration, melanin synthesis, and cross-linking collagen. Copper is an integral part of the antioxidant enzyme, copper-zinc superoxide dismutase (Cu, Zn-SOD), and has a role in iron homeostasis as a cofactor in ceruloplasmin. List of some of the major enzymes containing copper and their functions are summarized below:
The transportation and metabolism of copper in living organisms is now the subject of much active research. Copper transport at the cellular level involves the movement of extracellular copper across the cell membrane and into the cell by a special transporter. In the bloodstream, copper is carried throughout the body by albumin, seruloplasmin, and other proteins. The majority of copper blood (or serum copper) is bound to seruloplasmin. The proportion of copper-bound seruloplasmin can range from 70-95% and differ between individuals, depending, for example, on hormonal cycles, seasons, and copper status. Intracellular copper is directed to enzyme synthesis sites that require copper and organelles by a special protein called metallochaperones. A set of carriers carry copper into the subcellular compartment. Certain mechanisms exist to release copper from the cell. Special transporters return excess copper that is not stored to the liver for additional storage and/or biliary excretion. These mechanisms ensure that free bound ionic copper is not possible in most populations (ie, those without copper metabolism defects).
Copper is imported into cells through the cell wall by a plasma membrane transport protein known as Copper Transporter 1, or Ctr1. Ctr1 quickly binds to the intracellular copper companion protein. Atox1 provides copper to secretory lines and docks with ATP7B ATPase copper carriers in the liver or ATP7A in other cells. ATP7B directs copper to a ceruloplasmin plasma or biliary excretion in concert with a newly discovered companion, Murr1, a protein lost in the copper toxicosis of the dog. ATP7A directs copper in the trans-Golgi tissue to the dopamine-beta-monooxygenase protein, peptidylglycine alpha-amidating monooxygenase, lysyl oxidase, and tyrosinase, depending on the cell type. CCS is a copper chaperone for Cu/Zn-superoxide dismutase that protects cells against reactive oxygen species; it provides copper in the cytoplasmic and intermitochondrial spaces. Cox17 sends copper to the mitochondria to cytochrome c oxidase through the Cox11, Sco1, and Sco2 chaperones. Other chaperone copper may be present and may include metallothione and amyloid precursor proteins (APP). Genetic and nutritional studies have illustrated the important properties of this copper binding protein.
Absorption
In copper mammals absorbed in the stomach and small intestine, although there appears to be differences between species with respect to the maximum absorption sites. Copper is absorbed from the stomach and duodenum in mice and from the lower small intestine in hamsters. Maximum copper absorption sites are unknown to humans, but are assumed to be upper gastric and bowel due to the rapid appearance of Cu64 in plasma after oral administration.
The absorption of copper ranges from 15-97%, depending on the content of copper, copper form, and dietary composition.
Various factors affect the absorption of copper. For example, copper absorption is enhanced by consumption of animal protein, citrate, and phosphate. Copper salts, including copper gluconate, copper acetate, or copper sulphate, are more readily absorbed than copper oxides. Increased levels of dietary zinc, as well as cadmium, high intake of phytate and simple sugars (fructose, sucrose) inhibit the absorption of the copper diet. Furthermore, low levels of copper diet inhibit the absorption of iron.
Some forms of copper are not soluble in stomach acid and can not be absorbed from the stomach or small intestine. Also, some foods may contain digested fibers that bind with copper. High zinc intake can significantly reduce copper absorption. Intake of vitamin C or iron extreme can also affect the absorption of copper, reminding us of the fact that micronutrients need to be consumed as a balanced mixture. This is one of the reasons why the extreme intake of a single micronutrient is not recommended. Individuals with chronic digestive problems may not be able to absorb enough copper, although the foods they eat are rich in copper.
Several copper transporters have been identified that can move copper across the cell membrane. Other copper bowel transporters may be present. Copper of intestinal uptake can be catalyzed by Ctr1. Ctr1 is expressed in all cell types so far investigated, including enterocytes, and catalyzing the transport of Cu 1 across the cell membrane.
Excess copper (as well as other heavy metal ions such as zinc or cadmium) may be bound to metallothionein and sequestered in enterocytic intracellular vesicles (ie, dominant cells in the small intestinal mucosa).
Distribution
The copper released from the intestinal cells moves into the serosal capillaries (ie, the thin membrane layer) where it binds albumin, glutathione, and amino acids in the blood portal. There is also evidence for a small protein, transcuprein, with a specific role in plasma copper transport. Some or all of these copper binding molecules can participate in copper serum transport. Copper from the portal circulation is mainly taken by the liver. Once in the heart, copper is inserted into proteins that require copper, which is then secreted into the blood. Most copper (70 - 95%) excreted by the liver is fed into ceruloplasmin, the main copper carrier in the blood. Copper is transported to extra-liver tissue by seruloplasmin, albumin and amino acids, or excreted into bile. By regulating copper release, the liver is given homeostatic control over extrahepatic copper.
Excression
Bile is the main route for copper excretion and is essential in controlling liver copper levels. Most copper fecal results come from biliary excretion; the remainder comes from copper and copper that is not absorbed from desquamated mucosal cells.
Maps Copper in health
Dietary recommendations
National and international organizations concerned with nutrition and health have standards for copper intake at levels considered sufficient to maintain good health. These standards are periodically changed and updated when new scientific data are available. Standards are sometimes different between countries and organizations.
Adult
The World Health Organization recommends a minimum intake of approximately 1.3 mg/day. These values ​​are considered sufficient and safe for most of the general population. In North America, the US Institute of Medicine (IOM) sets the Recommended Dietary Allowance (RDA) for copper for healthy men and women with 0.9 mg/day. As for safety, IOM also sets the level of intake of Tolerable (ULs) for vitamins and minerals when the evidence is sufficient. In the case of copper, UL is set at 10 mg/day. The European Food Safety Authority reviewed the same security question and set its UL at 5 mg/day.
Teenagers, children and babies
The World Health Organization has not yet developed the minimum daily intake for this age group. In North America, the RDA is as follows: 0.34 mg/day for children 1-3 years; 0.44 mg/day for 4-8 years; 0.7 mg/day for 9-13 years; and 0.89 mg/day for 14-18 years. UL is: 1 mg/day for children 1-3 years; 3 mg/day for 4-8 years; 5 mg/day for 9-13 years; and 8 mg/day for 14-18 years.
Premature and premature infants are more sensitive to copper deficiency than adults. Because the fetus accumulates copper during the last 3 months of pregnancy, premature babies do not have enough time to store copper reserves in their liver and therefore require more copper at birth than the term infant.
For term infants, North America recommends a safe and adequate intake of about 0.2 mg/day. For premature infants, it is much higher: 1 mg/day. The World Health Organization has recommended the same minimum intake and suggests that premature infants be given formulas equipped with extra copper to prevent the development of copper deficiency.
Pregnant and lactating women
In North America, IOM has established an RDA for pregnancy at 1.0 mg/day and for lactation at 1.3 mg/day. The European Food Safety Authority (EFSA) refers to a collection of collective information as a Dietary Reference Value, with a Population Reference Intake (PRI) not an RDA. PRI for pregnancy was 1.6 mg/day, for lactation 1.6 mg/day - higher than the US RDA.
Food source
Copper is an important mineral that can not be formed by the human body. It must be ingested from food sources.
Food contributes to almost all copper consumed by humans. The best sources of food include seafood (especially shellfish), organ meats (eg, liver), grains, peas (eg peanuts and lentils) and chocolate. Nuts, including nuts and pecan nuts, are very rich in copper, such as whole grains such as wheat and rye, and some fruits including lemons and raisins. Other sources of food containing copper include cereals, potatoes, peas, red meat, mushrooms, some dark green leafy vegetables (like kale), and fruits (coconut, papaya and apple). Tea, rice and chicken are relatively low in copper, but can provide a reasonable amount of copper when consumed in significant amounts.
Eating a balanced diet with different foods from different food groups is the best way to avoid copper deficiency. In developed and developing countries, adults, young children and adolescents who eat foods from grains, millet, tubers or rice with peas (beans) or small quantities of fish or meat, some fruits and vegetables, and some vegetable oils are likely to get enough copper if their total food intake is sufficient in calories. In developed countries where consumption of red meat is high, copper intake also tends to be adequate.
As a natural element in the earth's crust, copper exists in most of the world's surface water and groundwater, although the actual concentration of copper in natural waters varies geographically. Drinking water can consist of 20-25% of copper food.
In many areas of the world, copper tubes delivering drinking water can be a source of copper food. The copper tube can snatch a small amount of copper, especially in the first year or two of its services. After that, a protective surface usually forms on the inside of a copper tube that inhibits the washing.
Supplementation
Copper supplements can prevent copper deficiency, but supplements should be taken only under the supervision of a doctor. Different forms of copper supplementation have different absorption rates. For example, copper absorption from copper oxide supplements is lower than copper gluconate, sulfate, or carbonate.
Supplementation is generally not recommended for healthy adults who consume a balanced diet that includes a wide variety of foods. However, supplementation under the care of doctors may be necessary for premature infants or those with low birth weight, infants fed unfortified formula milk or cow's milk during the first year of life, and malnourished children. Doctors may consider copper supplementation for 1) a disease that reduces digestion (eg, children with frequent diarrhea or infection, alcoholics), 2) inadequate food consumption (eg, elderly, weak people, those with eating disorders or diet), 3) patients taking drugs that block the use of copper by the body, 4) anemic patients treated with iron supplements, 5) anyone taking zinc supplements, and 6) those suffering from osteoporosis.
Many popular vitamin supplements include copper as small inorganic molecules such as copper oxide. This supplement can produce excessive copper in the brain because copper can cross the blood-brain barrier directly. Typically, organic copper in food is first processed by the liver that keeps the copper level under control.
Copper deficiency and excessive (non-genetic) health conditions
If the amount of copper is not adequately digested, the copper reserves in the liver will become exhausted and copper deficiency leads to disease or tissue injury (and in extreme cases, death). The toxicity of copper deficiency can be treated with a balanced diet or supplementation under a doctor's supervision. Conversely, like all substances, excess copper intake at levels far above the World Health Organization's boundaries can be toxic. Acute copper toxicity is generally associated with unintentional consumption. These symptoms subside when high copper food sources are no longer ingested.
In 1996, the International Program on Chemical Security, a related body of the World Health Organization, stated "there is a greater risk of health effects due to copper deficiency than to excess copper intake." This conclusion is confirmed in the most recent multi-route exposure survey.
The health conditions of non-genetic copper deficiency and copper excess are described below.
Copper deficiency
There are conflicting reports about the level of deprivation in the US. One review showed about 25% of teenagers, adults, and people over 65, did not meet the Recommended Dietary Allowance for copper. Another source states less commonly: federal survey of food consumption determined that for women and men over the age of 19 years, the average consumption of food and beverages were 1.11 and 1.54 mg/day, respectively. For women, 10% consume less than the Estimated Needs Average, for men less than 3%.
Recent copper deficiency has been implicated in the onset of progressive adult myeloneuropathy and in the development of severe blood disorders including myelodysplastic syndrome. Fortunately, copper deficiency can be confirmed by very low serum and ceruloplasmin concentrations in the blood.
Other conditions associated with copper deficiency include osteoporosis, osteoarthritis, rheumatoid arthritis, cardiovascular disease, colon cancer, and chronic conditions involving bone, connective tissue, heart and blood vessels. the nervous system and the immune system. Copper deficiency alters the role of other cellular constituents involved in antioxidant activity, such as iron, selenium, and glutathione, and therefore plays an important role in the disease in which oxidant stress increases. Minor copper deficiency, ie, mild, believed to be wider than previously thought, can damage human health in a subtle way.
Populations prone to copper deficiency include those with genetic defects for Menkes disease, low birth weight infants, infants fed non-breast milk or formula milk, pregnant and lactating women, patients receiving total parenteral nutrition, individuals with "malabsorption syndrome" (impaired absorption food), diabetics, individuals with chronic diseases that result in low food intake, such as alcoholics, and people with eating disorders. Parents and athletes are also at higher risk for copper deficiency because of the special needs that increase daily needs. Vegetarians may experience a decrease in copper intake due to the consumption of plant foods where the bioavailability of copper is low. Fetuses and baby girls with severe copper deficiency have an increased risk of low birth weight, muscle weakness, and neurological problems. Copper deficiency in this population can cause anemia, bone abnormalities, growth disorders, weight gain, frequent infections (colds, flu, pneumonia), poor motor coordination, and low energy.
Excess copper
Excess copper is the subject of much current research. Differences have emerged from the study that copper excess factors differ in normal populations compared with increased susceptibility to adverse events and those with rare genetic disease. This has led to statements from health organizations that can be confusing to the uninitiated. For example, according to a US Institute of Medicine report, the level of copper intake for a significant percentage of the population is lower than the recommended rate. On the other hand, the US National Research Council concluded in its Copper in Drinking Water report that there is concern for copper poisoning in the vulnerable population and recommended that additional research be undertaken to identify and characterize copper-sensitive populations.
Excessive copper intake causes abdominal pain, nausea, and diarrhea and can cause tissue injury and disease.
Potential oxidation of copper may be responsible for some of its toxicity in case of excessive consumption. At high concentrations, copper is known to cause oxidative damage to biological systems, including lipid peroxidation or other macromolecules.
While the cause and development of Alzheimer's disease is not well understood, research shows that, among other key observations, iron, aluminum, and copper accumulate in the brains of Alzheimer's patients. However, it is not known whether this accumulation is the cause or consequence of the disease.
Research has been going on for the last two decades to determine whether copper is the cause or agent of Alzheimer's disease prevention. For example, as a possible causative agent or expression of metallic homeostatic disorders, studies have shown that copper may play a role in increasing the growth of clump proteins in the brain of Alzheimer's disease, possibly by destroying molecules that remove the toxic buildup of amyloid beta. (A?) In the brain. There is a relationship between a diet rich in copper and iron along saturated fats and Alzheimer's disease. On the other hand, studies have also shown a beneficial role of copper in treating rather than causing Alzheimer's disease. For example, copper has been shown to 1) promote the non-amyloidogenic protein process of beta amyloid precursor (APP), thereby decreasing the production of amyloid beta (A?) In cell culture system 2) increasing life span and decreasing dissolved amyloid production in transgenic APP mice; 3) lowering A? levels in the cerebral spinal fluid in patients with Alzheimer's disease.
Furthermore, long-term copper treatment (oral intake of 8 mg copper (Cu- (II) -orotate-dihydrate) was excluded as a risk factor for Alzheimer's disease in human clinical trials and a potentially beneficial role of copper in Alzheimer's disease has been shown in bone liquid levels behind the brain A? 42, toxic peptides and disease biomarkers. More research is needed to understand the disruption of metallic homeostasis in patients with Alzheimer's disease and how to overcome this disorder therapeutically. Because this experiment uses Cu- (II) -orotate-dihydrate, it is not related to the effects of copper oxide in supplements.
Copper poisoning from excessive exposure
In humans, the liver is the main organ of copper induced toxicity. Other target organs include bone and nervous system and immune system. Excessive copper intake also induces indirect toxicity by interacting with other nutrients. For example, excessive copper intake produces anemia by disrupting transport and/or iron metabolism.
The identification of genetic disorders of copper metabolism causes severe copper toxicity (ie, Wilson's disease) has propelled the research into molecular genetics and biology of copper homeostasis (for more information, see the following section on copper genetic disease). Much attention is focused on the potential consequences of copper toxicity in normal and potentially vulnerable populations. Potentially vulnerable subpopulations include hemodialysis patients and individuals with chronic liver disease. Recently, concerns are expressed about the potential sensitivity to individual liver disease that is a heterozygous carrier of the genetic disorders of Wilson's disease (ie, those with one normal ATPase Wilson gene and one mutation) but who do not have the disease (requiring defects in both genes relevant). However, to date, no data is available that supports or refutes this hypothesis.
Acute exposure
In the case of human reports intentionally or unintentionally ingesting a high concentration of copper salt (the dose is usually unknown but reported to be 20-70 grams of copper), the development of observed symptoms includes abdominal pain, headache, nausea, dizziness, vomiting and diarrhea. , tachycardia, respiratory difficulty, haemolytic anemia, haematuria, massive gastrointestinal hemorrhage, liver and kidney failure, and death.
Episodes of acute gastrointestinal disturbance after ingestion of single or recurrent drinking water containing copper levels (generally above 3-6 mg/L) are characterized by nausea, vomiting, and gastric irritation. These symptoms disappear when copper in the drinking water source is reduced.
Three experimental studies were performed that showed a threshold for acute gastrointestinal disturbances of about 4-5 mg/L in healthy adults, although it is unclear from these findings whether the symptoms are caused by acute irritant effects of copper and/or metallic, bitter, salty taste. In an experimental study with healthy adults, the mean flavor threshold for copper sulphate and chloride in tap water, deionized water, or mineral water was 2.5-3.5 mg/L. This was just below the experimental threshold for disturbance acute digestion.
Chronic exposures
Long term copper toxicity has not been well studied in humans, but rarely occurs in normal populations that do not have congenital defects in copper homeostasis.
There is little evidence to suggest that chronic human exposure to copper produces a systemic effect other than a liver injury. Chronic copper poisoning that causes liver failure is reported in young adult males who are not known to have a genetic susceptibility that consumes 30-60 mg/day of copper as a mineral supplement for 3 years. Individuals living in US households supplied with tap water containing & gt; 3 mg/L of copper showed no adverse health effects.
No effect of copper supplementation on serum liver enzymes, oxidative stress biomarkers, and other biochemical endpoints has been observed in healthy young human volunteers given daily doses of 6 to 10 mg/day of copper up to 12 weeks. Infants aged 3-12 months who consumed water containing 2 mg Cu/L for 9 months did not differ from the concurrent control group on gastrointestinal tract symptoms (GIT), growth rates, morbidity, serum liver enzymes and bilirubin levels, and other biochemical endpoints. Ceruloplasmin serum increased temporarily in the infant group exposed at 9 months and was similar to control at 12 months, indicating homeostatic adaptation and/or ripening of homeostatic response.
Dermal exposure has not been associated with systemic toxicity but anecdotal reports of allergic responses may be sensitization to nickel and cross-reaction with copper or skin irritation from copper. Workers exposed to high levels of air copper (thus estimated intake of 200 mg Cu/day) show signs that indicate copper toxicity (eg, elevated serum copper levels, hepatomegaly). However, other exposures that occur along with pesticide agents or in mining and smelting may contribute to this effect. The effects of copper inhalation are being thoroughly investigated by industry-sponsored programs in the workplace and worker safety. This multi-year research effort is expected to be completed in 2011.
High copper status measurements
Although a number of indicators are useful in diagnosing copper deficiency, there is no reliable biomarker of copper excess resulting from dietary intake. The most reliable indicator of excess copper status is the concentration of liver copper. However, the measurement of this endpoint in humans is intrusive and is generally not done except in case of suspected copper poisoning. Increased serum levels of copper or ceruolplasmin can not be reliably related to copper toxicity because increased concentrations can be caused by inflammation, infection, disease, malignancy, pregnancy, and other biological stressors. The level of copper-containing enzymes, such as cytochrome c oxidase, superoxide dismutase, and diaminase oxidase, varies not only in response to copper states but also in response to other physiological and biochemical factors and is therefore an inconsistent marker of excess copper status.
Biomarkers of new candidates for copper excess and deficiency have emerged in recent years. This potential marker is a companion protein, which delivers copper to the SOD1 antioxidant protein (copper, zinc superoxide dismutase). This is called "copper chaperone for SOD1" (CCS), and excellent animal data supports its use as a marker in accessible cells (eg, erythrocytes) for copper deficiency and overload. CCS is currently being tested as a biomarker in humans.
Hereditary copper metabolic diseases
Some rare genetic diseases (Wilson's disease, Menkes disease, idiopathic copper toxicosis, Indian children's cirrhosis) are associated with improper copper utilization in the body. All of these diseases involve mutations of genes containing the genetic code for the production of specific proteins involved in the absorption and distribution of copper. When this protein is dysfunctional, a good copper build in the liver or the body fails to absorb copper.
These diseases are inherited and can not be obtained. Adjusting the levels of copper in food or drinking water will not cure this condition (although therapy is available to manage symptoms of genetic copper excess disease).
The study of copper metabolic disease and its associated proteins allows scientists to understand how the human body uses copper and why it matters as an essential micronutrient.
The disease arises from defects in two similar copper pumps, Menkes and Wilson Cu-ATPase. The Menkes ATPase is expressed in tissues such as skin-forming fibroblasts, kidneys, placenta, brain, intestines and vascular system, while Wilson ATPase is expressed primarily in the liver, but also in the mammary gland and possibly in other specialized tissues. This knowledge leads the scientist toward a possible cure for genetic copper disease.
Menkes Disease
Menkes disease, the genetic condition of copper deficiency, was first described by John Menkes in 1962. It is a rare X-linked disorder affecting about 1/200,000 live births, especially boys. Patients with Liver of Menkes disease can not absorb the essential copper needed for the patient to survive. Death usually occurs in early childhood: most affected individuals die before the age of 10, although some patients have survived into adolescence and early 20s.
Proteins produced by the Menkes gene are responsible for transporting copper across the gastrointestinal (GIT) mucosa and blood-brain barrier. Mutation defects in genes encoding copper ATPase cause copper to remain trapped in the lining of the small intestine. Therefore, copper can not be pumped out of the intestinal cells and into the blood to be transported to the liver and consequently for the rest of the body. Therefore, this disease resembles a severe deficiency of copper nutrients despite adequate copper consumption.
Symptoms of the disease include coarse, brittle, depigmented and other neonatal problems, including the inability to control body temperature, mental retardation, bone damage, and abnormal connective tissue growth.
Menkes patients exhibit severe neurological disorders, apparently due to the lack of some copper-dependent enzymes necessary for brain development, including reduced cytochrome c oxidase activity. Smooth and curly-looking bronze hipopigmented hair is caused by a deficiency in an unknown cuproenzyme. Reduced lysine oxidase activity results in damaged collagen and elastin polymerization and associated connective tissue abnormalities including aortic aneurysms, loose skin, and fragile bone.
With an early diagnosis and treatment consisting of daily intraperitoneal and intrathecal copper injections into the central nervous system, severe neurological problems can be avoided and prolonged survival. However, patients with Menkes disease maintain abnormal bone abnormalities and connective tissue and exhibit mild to severe mental retardation. Even with early diagnosis and treatment, Menkes disease is usually fatal.
Ongoing research on Menkes disease leads to a greater understanding of copper homeostasis, the biochemical mechanisms involved in the disease, and possible ways to treat it. Investigation of copper transport across the blood/brain barrier, based on genetically modified mice studies, is designed to help researchers understand the root causes of copper deficiency in Menkes disease. The genetic makeup of "transgenic mice" is altered in a way that helps researchers collect new perspectives on copper deficiency. Research to date is valuable: genes can be 'switched off' gradually to explore different levels of deficiency.
The researchers also showed in a DNA-damaging reaction tube in the cells of the Menkes patient that it can be repaired. In time, the procedure necessary to repair the damaged gene in the human body can be found.
Wilson's disease
Wilson's disease is a rare autosomal recessive (chromosome 13) genetic disorder of copper transport that causes excess copper to accumulate in the liver. It produces liver toxicity, among other symptoms. The disease is now treatable.
Wilson's disease is produced by defective protein mutations transporting copper from the liver to bile for excretion. The disease involves poor copper incorporation into ceruloplasmin and impaired biliary copper excretion and is usually caused by mutations that impair Wilson's copper ATPase function. This genetic mutation produces copper toxins due to excessive copper accumulation, especially in the liver and brain and, to a lesser extent, in the kidneys, eyes, and other organs.
This disease, which affects about 1/30,000 infants of both sexes, may become clinical evidence at all times from infancy to early adulthood. The age of onset of Wilson's disease ranges from 3 to 50 years. Early symptoms include liver, neurological, or psychiatric disorders and, rarely, kidney, bone, or endocrine symptoms. The disease develops with more severe jaundice and the development of encephalopathy, severe coagulation abnormalities, sometimes associated with intravascular coagulation, and terminal renal insufficiency. Typical types of tremor in the upper extremities, movement slowness, and temperament changes become apparent. The Kayser-Fleischer Ring, a rusty brown shift on the outer edge of the iris due to copper deposition recorded in 90% of patients, becomes evident when copper begins to accumulate and affect the nervous system.
Almost always, death occurs if the disease is not treated. Fortunately, the identification of mutations in the Wilson ATPase gene underlying most cases of Wilson's disease has made DNA testing possible for diagnosis.
If diagnosed and treated early enough, patients with Wilson's disease can live long and productively. Wilson's disease is administered by copper chelation therapy with D-penicillamine (which picks up and binds copper and allows the patient to remove excess copper accumulated in the liver), therapy with zinc sulfate or zinc acetate, and restrictive dietary intake, such as elimination. chocolate, oysters, and mushrooms. Zinc therapy is now a treatment option. Zinc produces mucosal blocks by inducing metallothionein, which binds copper in mucosal cells until they are peeled and eliminated in the feces. and it competes with copper for absorption in the gut by DMT1 (Divalent Metal transporter 1). More recently, experimental treatment with tetrathiomolybdate showed promising results. Tetrathiomolybdate appears to be an excellent form of early treatment in patients with neurologic symptoms. In contrast to penicillamine therapy, initial treatment with tetrathiomolybdate rarely allows further neurologic deterioration, often irreparable.
More than 100 different genetic defects that led to Wilson's disease have been described and made available on the Internet at [1]. Some mutations have geographical groupings.
Many Wilson patients carry different mutations on each of the 13 chromosomes (ie, they are multiple heterozygotes). Even in individuals who are homozygous for mutations, the onset and severity of the disease may vary. Homozygous individuals for heavy mutations (eg, who cut protein) have earlier disease onset. The severity of the disease can also be a function of environmental factors, including the amount of copper in the diet or variability in other protein functions that affect the copper homeostasis.
It has been suggested that heterozygous carriers of the Wilson disease gene mutation may be potentially more susceptible to an increase in copper intake than the general population. The heterozygous frequency of 1/90 people has been estimated in the entire population. However, there is no evidence to support this speculation. Furthermore, a review of data on single-alleles autosomal recessive diseases in humans does not indicate that heterozygous carriers are likely to be affected by changes in their genetic status.
Other diseases in which abnormalities in copper metabolism appear to be involved include Indian child cirrhosis (ICC), endemic Tyrolean endemic endemic (ETIC), and idiopathic copper toxicosis (ICT), also known as non-Indian child cirrhosis. ICT is a recognized genetic disease in the early twentieth century especially in the Tyrolean region of Austria and in the Pune region of India.
ICC, ICT, and ETIC are similar infant syndromes in their etiology and presentation. Both appear to have a genetic component and contribute to an increase in copper intake.
In the case of ICC, increased copper intake is caused by heating and/or storing milk in copper or brass vessels. The case of ICT, on the other hand, is due to the high concentration of copper in the water supply. Although exposure to high copper concentrations is usually found in both diseases, some cases occur in exclusively breast-fed children or who receive only low copper levels in the water supply. The current hypothesis is that ICT is caused by genetic lesions resulting in impaired copper metabolism combined with high copper intake. This hypothesis is supported by the frequency of occurrence of parental consanguinity in most of these cases, which is absent in areas with increased copper in drinking water and where these syndromes do not occur.
ICTs seem to disappear as a result of greater genetic diversity in the affected populations in relation to educational programs to ensure that canned cooking utensils are used instead of pots and copper pans that are directly exposed to cooked food. The dominance of early-child cirrhosis cases identified in Germany over a 10-year period is not associated with an external source of copper or with high concentrations of liver metals. Only occasional cases of spontaneous ICT appear today.
Cancer
Cancer is a complicated illness that is not well understood. Some researchers are investigating the possible role of copper in angiogenesis associated with various types of cancer. A copper chelator, tetrathiomolybdate, which depletes the supply of copper in the body, is being investigated as an anti-angiogenic agent in trials and clinical trials. These drugs can inhibit tumor angiogenesis in hepatocellular carcinoma, pleural mesothelioma, colorectal cancer, squamous carcinoma of the head and neck, breast cancer, and kidney cancer. Copper complex of synthetic salicylaldehyde pyrazole hydrazone (SPH) derivative induced apoptosis human umbilical endothelial cell (HUVEC) and demonstrated in vitro anti-angiogenesis effect.
Copper trace elements have been found to promote tumor growth. Some evidence from animal models suggests that the tumor concentrates high levels of copper. Meanwhile, extra copper has been found in some human cancers. More recently, therapeutic strategies that target copper in tumors have been proposed. After administration with a certain copper chelator, a copper complex will form at a relatively high level in the tumor. Copper complexes are often toxic to cells, therefore tumor cells die, while normal cells throughout the body stay alive for lower copper levels.
Some copper chelators get more effective or new bioactivity after forming a copper-chelator complex. It was found that Cu2 is needed to induce apoptosis PDTC in HL-60 cells. The benzoylhydrazone salicylaldehyde copper (SBH) copper complex exhibits increased efficacy inhibiting growth in some cancer cell lines, when compared with metal-free SBHs.
Tri can react with various types of transition metal cations and thus form a number of complexes. The more complex cytotoxic copper-complex complex than other transitional metal complexes in MOLT-4 cells, existing human T cell cells leukemia cells. Trial, especially their copper complex appears to be a strong inhibitor of DNA synthesis and cell growth in several lines of human cancer cells, and mouse cancer cell lines.
Salicylaldehyde pyrazole hydrazone (SPH) derivatives were found to inhibit the growth of A549 lung cell carcinoma. SPH has identical ligands for Cu2 as SBH. The Cu-SPH complex was found to induce apoptosis in A549, H322 and H1299 lung cancer cells.
Contraception with copper IUD
Intrauterine copper contraceptives (IUDs) are a type of long-acting reversible contraceptive that is considered to be one of the most effective forms of birth control. It is also regarded as the most effective non-hormonal contraceptive. The main working mechanism of copper IUD is to prevent fertilization. The active substance released from the IUD, together with products derived from the inflammatory reaction present in the luminal fluid of the genital tract, is toxic to spermatozoa and oocytes, preventing healthy gamete encounters and the formation of live embryos.
Plant and animal health
In addition to being an essential nutrient for humans, copper is essential for animal and plant health and plays an important role in agriculture.
Plant health
Copper concentration in soil is not uniform across the world. In many areas, the soil has insufficient copper levels. Soils that are naturally deficient in copper often require copper supplements before agricultural crops, such as cereals, can grow.
Copper deficiency on the ground can lead to crop failure. Copper deficiency is a major problem in global food production, resulting in a loss in yield and reducing the quality of output. Nitrogen fertilizers can aggravate copper deficiency in farmland.
Two of the most important food crops, rice, and wheat in the world, are particularly vulnerable to copper deficiency. So do some other important foods, including oranges, oats, spinach and carrots. On the other hand, some foods include coconut, soy and asparagus, not too sensitive to copper-deficient soils.
The most effective strategy to combat copper deficiency is to equip the soil with copper, usually in the form of copper sulfate. Sludge waste is also used in some areas to fill agricultural land with organic and metal traces, including copper.
Animal health
In cattle, cattle and sheep generally indicate when they lack copper. Swayback, the sheep's disease associated with copper deficiency, imposes huge costs for farmers around the world, especially in Europe, North America, and many tropical countries. For pigs, copper has proven to be a remarkable growth promoter.
See also
- Nutrition
- dietary minerals
- Essential nutrients
- Micronutrients
- List of micronutrients
References
Source of the article : Wikipedia
0 Comments